Michelle Leviov

The management of metastatic spinal cord compression: A radiotherapeutic success ceiling

PURPOSE In assessing the effectiveness of the management of metastatic spinal cord or cauda equina compression, we performed a retrospective analysis of 70 patients with this complication whom we treated from 1985 to 1989. METHODS AND MATERIALS The most frequent primary diagnoses in our series were carcinomas of unknown origin and of the breast, lymphoproliferative disease, lung cancer, and prostatic carcinoma. We used the Findlay classification to group all patients according to their pre-therapeutic functional motor status as Grade I (24 patients or 34%), Grade II (27, or 39%) or Grade III (19 or 27%). Treatment consisted of 30-45 Gy of irradiation (using two different schedules) together with high-dose dexamethasone; in only five cases was there surgical intervention. RESULTS We found that a powerful predictor of response to radiotherapy was the patients neurologic status (Findlay grade) at the time of diagnosis: 66% of previously ambulatory patients remained so, whereas 30% of non-ambulatory patients and only 16% of paraplegic patients regained the ability to walk. Another important predictor of response was primary tumor histology, with the most favorable responses to radiation therapy having been observed in lymphoproliferative diseases and in breast cancer, but with some response in other radiosensitive malignancies as well. CONCLUSION The similarity of our results to those of other centers leads us to conclude that a radiotherapeutic success ceiling of 80% may have been reached for Findlay Grade I patients with metastatic spinal cord compression. In view of this, we suggest that future therapeutic endeavour would be best directed toward early diagnosis of the condition.

Intermediate and High-Grade Gastric Non-Hodgkin's Lymphoma: A Prospective Study of Non-Surgical Treatment with Primary Chemotherapy, with or without Radiotherapy

The role of surgery as initial treatment in gastric lymphoma remains controversial. We have prospectively evaluated a stomach conservation strategy in histologically aggressive gastric lymphoma, using primary adriamycin-containing chemotherapy, followed by involved-field radiotherapy in patients with limited disease. Twenty-six patients (median age 69 years) were entered in this study; 15 had stage I disease, 7 had stage II disease and 4 had stage IV disease. The chemotherapy combinations were CHOP (18 patients) and ProMACE/MOPP (8 patients). Radiotherapy was given to 11 patients. Of the 24 patients evaluated for response, 18 (75%) achieved endoscopically-confirmed complete response and 4 (17%) partial response. During follow-up (median 22 months), none of the complete responders developed recurrent lymphoma. Gastric resection was performed in 1/26 patients who did not respond to primary chemotherapy. There were no cases of perforation, but three patients (12%) developed acute gastro-intestinal bleeding a few days after the onset of chemotherapy, one of whom required a surgical devascularization procedure. There was no treatment-related mortality. These data further support the non-surgical approach in histologically aggressive gastric lymphoma, using primary chemotherapy with or without radiation therapy.

Haptoglobin-related protein as a serum marker in malignant lymphoma.

A novel serum 21 kDa haptoglobin-related protein (Hpr) was investigated in patients with malignant lymphoma, to evaluate its correlation with clinical and histologic features at presentation and its possible role as a tumor marker for patient outcome. One hundred fifty eight serum samples were taken from 88 patients with non-Hodgkin’s lymphoma (n=58) and Hodgkin’s disease (n=30) at presentation and in the course of follow-up. Sera from 61 healthy volunteers served as normal controls. Serum Hpr levels in the lymphoma patients (median 430xl03 u/ml, range 0-4000xl03) were significantly higher than in the control group (median 68xl03 u/ml, range 0-180xl03) (p=0.0001). Higher median Hpr values were detected in patients with advanced disease (p=0.013), “B” symptoms (p=0.029) and in males (p=0.053). There was also a significant correlation between Hpr and erythrocyte sedimentation rate (p=0.028). Serial determinations showed a significant decrease of the initial Hpr values obtained after treatment in 41 patients, 38 of whom achieved complete remission. In the follow-up period additional Hpr measurements were taken from 17 patients. Three of them eventually relapsed, and showed increased Hpr levels at the time of relapse. Hpr levels remained low in 11 of 14 patients who maintained complete remission, and increased in three. In conclusion, serum Hpr is a new serum tumor marker of potential use in the clinical setting of lymphoma.

Dexamethasone, etoposide, ifosfamide, and cisplatin as second-line therapy in patients with aggressive non-hodgkin's lymphoma

This study analyzed the long term results of a combination of dexamethasone, etoposide, ifosfamide, and cisplatin (DVIP) used at the study center as standard second‐line combination therapy in patients with aggressive non‐Hodgkins lymphoma (NHL) after prior exposure to doxorubicin.

Total Skin Electron Irradiation: Efficacy in Early Mycosis Fungoides

The rare, indolent, but lethal malignancy, mycosis fungoides (MF), is amenable to durable remissions if treated topically at an early stage with nitrogen mustard, PUVA, or radiotherapy. A modification of conventional therapeutic irradiation which utilizes electron beams rather than photons, has been in use since 1951. This method, termed total skin electron irradiation (TSEI), has achieved consistently good CR rates (95-100%) at a variety of centres in the U.S.A., England, France, and Italy, despite troublesome differences in staging systems. In northern Israel we have treated 37 MF patients with TSEI during the past 13 years. All 21 of our early stage patients achieved CR, which is no longer regarded as an unusual result. However, most workers in the field acknowledge that issues of optimal dosing and curative potency remain unresolved.

Total Skin Electron Irradiation in Mycosis Fungoides Dose and Fractionation Considerations

This study was undertaken to analyze the influence of total skin dose and dose-fractionation schedules on the response rate, survival and skin toxicity of patients with mycosis fungoides [MF] treated with total skin electron irradiation [TSEI]. From 1979 to 1992, 40 patients with MF were treated with TSEI using a modified Christie Hospital technique. Mean follow-up time was 48 months [median 20 months]. 37/40 patients completed TSEI; three died due to non-treatment-related conditions during therapy. 34/37 [92%] treated patients achieved complete remission [CR] and 16/40 [40%] are alive with no evidence of disease. Over the years, changes in dose-fractionation schedules were made and correlated with the pattern of CR and skin toxicity. The 5-year actuarial survival [Stanford staging] was 84% in Stages IA-IB [all Stage IA patients are alive] and 59% in Stage II. The probability of survival of Stage III-IV patients was 30% at 30 months. Late skin toxicity was mild to moderate in 60% and severe in 25% of patients. A reduction of the total dose and dose-per-fraction resulted in an acceptable CR rate and a significantly lower toxicity. TSEI is effective in early stage MF. Skin control and late skin toxicity seem to be dose-fractionation-schedule related. For the early stages, the optimal treatment schedule seems to be 24-30 Gy to the whole skin surface in 2.4-3.0 Gy fractions, given twice weekly over a period of four to six weeks. Total doses of 24-30 Gy at 2.4-3.0 Gy per fraction yielded comparable skin control rates with lower skin toxicity.

Radiation-induced tumors in irradiated stage I testicular seminoma: Results of a 25-year follow-up (1968–1993)

Testicular seminoma is a very radiosensitive and curable cancer, with survival rates following radiation therapy within the range of 90–98% without apparent severe side effects. However, long‐term survival following exposure to moderate‐dose radiation therapy can result in radiation‐induced tumors.

Short-term complications of intra-operative radiotherapy for early breast cancer

IORT is becoming an accepted radiotherapy technique for treatment of early breast cancer. Data regarding the early complications of breast IORT are lacking.

Benign proliferative lesions mimicking recurrence of Hodgkin's disease

Salvage treatment in patients with recurrent Hodgkins disease is more effective when tumor burden is minimal. That is why more intensive follow-up strategies, including frequent imaging tests, have been recently developed for the detection of early relapse. However, as screening procedures become more sensitive, there is an increasing risk of false-positive results, demonstrating nonmalignant proliferative disorders. We describe three young patients who had lymphocyte-predominant or mixed-cellularity Hodgkins disease and were in clinical complete remission for 2.5-3 years after a combined treatment with chemotherapy and radiation. Imaging tests revealed new gallium-avid lymphadenopathy in the chest in two cases. Pathologically enlarged pelvic lymph nodes were identified in another case, after a diagnosis of recurrent disease in axilla. Those findings were interpreted as relapse, and the patients underwent thoracotomy and laparotomy, respectively, for histologic confirmation. The results showed progressively transformed germinal centers and sarcoid-like lesions, two benign proliferative disorders. When patients with Hodgkins disease in remission show new lymphadenopathy, even with positive gallium scan, it seems mandatory to obtain tissue for histologic examination, even through invasive procedures such as laparotomy and thoracotomy, to avoid wrong diagnosis and unnecessary treatment.

Radiation-induced sarcoma following curative radiotherapy for testicular seminoma: case report and brief review of the literature.

We report a case of radiation-induced retroperitoneal leiomyosarcoma which developed 37 years after the patient received radiation therapy for testicular seminoma. The sarcoma originated within the para-aortic field, extensively involving neighboring organs, soft tissue and muscle tissues, and could be only partially resected. The absolute number of these secondary sarcomas is low, but the risk of developing such neoplasms calls for awareness in the long-term follow-up of cured seminoma patients.